Researchers have identified a shortlist of 89 FDA-approved antiviral drugs and 39 plant-derived molecules that show potential for blocking SARS-CoV-2 replication through computational modeling. The study, published this week in Green Technology, Resilience, and Sustainability, uses molecular docking to predict which compounds best bind to three critical viral proteins to prepare for future pandemic responses.
This in silico research—meaning it was conducted via computer simulation rather than in a living organism—serves as a proactive blueprint for drug repurposing. By identifying molecules that can physically “plug” the active sites of viral proteins, scientists can significantly shorten the timeline for developing new treatments. Bioengineer.org reported that such strategies can reduce drug development cycles from over a decade to just three to six years, while cutting costs by up to 60 percent.
How Computational Docking Predicts Viral Interference
The study, led by Triveni Singirisetty and colleagues, focused on three specific targets within the SARS-CoV-2 life cycle. Each target represents a different stage of how the virus replicates and matures inside a human cell. The team used the Schrödinger 2021_2 Glide Maestro tool to simulate how well various compounds “dock” into the crystal structures of these proteins.
- Nsp15 (Endoribonuclease): A protein that cleaves RNA, essential for the virus to process its genetic material. It requires metal ions like manganese to function.
- Main Protease: A central enzyme responsible for processing viral polyproteins, effectively acting as the “molecular scissors” that allow the virus to build its components.
- Nsp16-Nsp10 Complex: This complex performs 2′-O-methyltransferase activity, which helps the virus “cap” its RNA to evade the host’s immune detection.
Molecules Show Potential for Drug Repurposing Through Mathematical Predictions
- This is not a cure: The results are mathematical predictions of how molecules might stick to a virus; they have not yet been tested in humans or animals.
- Drug repurposing is the goal: The study looks at existing, safe drugs (like remdesivir or zidovudine) to see if they can be used in new ways, saving years of research.
- Plant compounds show promise: Several natural molecules, such as quercetin and apigenin, showed strong binding potential, suggesting they warrant further laboratory testing.
Predicted Binding Strengths Across Viral Targets
The researchers ranked compounds based on “glide scores” and binding energy, measured in kilocalories per mole (kcal/mol). A more negative value generally indicates a more stable and potentially effective interaction between the drug and the protein. While remdesivir is a well-known antiviral, the simulation suggested other compounds might offer even stronger binding profiles in specific contexts.
| Target Protein | Top Antiviral Leads (Predicted) | Top Plant-Derived Leads (Predicted) |
|---|---|---|
| Nsp15 | Remdesivir, Ribavirin, Letermovir | Epigallocatechin, Amentoflavone, Quercetin |
| Main Protease | Adefovir, Entecavir, Penciclovir | Ent-epiafzelechin, Hippomannin A, Proanthocyanidin |
| Nsp16-Nsp10 | Zidovudine, Vidarabine, Tenofovir | Apigenin, Quercetin, Silymarin |
One notable finding was the performance of zidovudine against the nsp16-nsp10 complex. The simulation recorded a binding energy of -80.07 kcal/mol, which was even more stable than the binding of S-adenosylmethionine (SAM), the natural molecule the protein typically interacts with. This suggests that zidovudine could potentially interfere with the virus’s ability to mask itself from the immune system.
The Path from Simulation to Clinical Application
While these results provide a vital “shortlist” for researchers, they face significant regulatory and scientific hurdles. The transition from in silico docking to human efficacy requires a rigorous multi-stage process. First, compounds must undergo in vitro testing (in lab dishes) to confirm they actually stop viral replication. This is followed by in vivo studies (in animal models) to assess safety and how the drug moves through a living system.
Regulatory bodies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require substantial evidence from Phase I, II, and III clinical trials before any repurposed drug can be administered to the general public. The primary challenge in repurposing is ensuring that the dosage required to inhibit the virus does not reach toxic levels in human tissue.
The researchers acknowledged that this study did not perform molecular dynamics simulations—complex calculations that show how molecules move over time—which are necessary to refine these predictions. The library of compounds was not exhaustive, meaning other potentially effective molecules may have been missed.
Avoid Self-Medicating with Antiviral Drugs or Plant Extracts
It is critical to note that none of the compounds mentioned in this research, including remdesivir, ribavirin, or plant-derived flavonoids, should be used to treat COVID-19 or any other viral infection without a direct prescription from a healthcare provider. Self-medicating with antiviral drugs or concentrated plant extracts can lead to severe side effects, drug-drug interactions, or toxicity. If you are experiencing symptoms of a respiratory infection, seek professional medical evaluation immediately.
The study serves as a strategic preparedness tool rather than a clinical recommendation. Its value lies in narrowing down thousands of possibilities to a manageable set of leads that laboratories can prioritize for experimental testing during the next viral outbreak.
References
- Singirisetty, T., et al. (2025). Drug repurposing in silico screening of antiviral drugs and evidence-based plant-derived anti-oxidant molecules targeting nsp15, main protease, and nsp16-nsp10 complex of SARS-CoV-2. Green Technology, Resilience, and Sustainability. https://doi.org/10.1007/s44173-025-00017-5
- World Health Organization (WHO) – COVID-19 Therapeutics guidance.
- Centers for Disease Control and Prevention (CDC) – Clinical manifestations of SARS-CoV-2.
